Frequency and Outcomes of Reduced Dose Non–Vitamin K Antagonist Anticoagulants: Results From ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II)

Abstract

BackgroundNon–vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice.Methods and ResultsWe analyzed data from the ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow‐up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P<0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P<0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced‐dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92‐2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86‐3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately.ConclusionsThe majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817.

Appropriateness of prescription of oral anticoagulant therapy in acutely hospitalized older people with atrial fibrillation. Secondary analysis of the SIM‐AF cluster randomized clinical trial

“…This is certainly due to the small number of clinical events which occurred in this short‐term follow‐up period. In the frame of the ORBIT‐AF II registry, including more than 6900 outpatients with AF, those inappropriately prescribed with reduced doses of DOACs had a higher risk of thromboembolic events and death . There is, however, a paucity of studies assessing the impact of appropriateness of OAC prescription on patient clinical outcomes, so that more studies are requested to drive stronger conclusions on this key clinical topic.…”

Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses

“…Overdosing was associated with significantly increased all-cause mortality whereas under-dosing was associated with increased cardiovascular hospitalizations [14]. A subsequent analysis of 7925 AF patients treated with DOACs from the same registry showed that 16% of patients were on reduced doses with many of these doses adjustments (57%) not following the recommended doses [15]. Nevertheless, after risk-adjustment, the use of lower-than-recommended dose resulted in similar thromboembolic and bleeding risk compared to appropriately dosed DOAC use [15].…”

Factors related to inappropriate edoxaban use

“…Edoxaban does not require regular monitoring, but diligent anthropometric measurement should be done at least once at the beginning of the edoxaban initiation as recommended by the manufacturer . The prescription with lower dose than the one of indicated would come from the concerns about occurrence of bleeding event, but some studies associated with dose appropriateness and clinical outcomes of DOACs have shown that the inappropriately low‐dosed DOAC group was at higher risk of thromboembolic event and death …”

“…18 The prescription with lower dose than the one of indicated would come from the concerns about occurrence of bleeding event, 22 but some studies associated with dose appropriateness and clinical outcomes of DOACs have shown that the inappropriately low-dosed DOAC group was at higher risk of thromboembolic event and death. 23,24…”